tbuckley/cabot-search huggingface dataset:
Abstract 14872: Lactate Promotes Endothelial-to-Mesenchymal Transition via Snail1 Lactylation After Myocardial Infarction
Authors: Min Fan, Kun Yang, Xiaohui Wang, P S Gill, Tuanzhu Ha, David Williams, Chuanfu Li
Journal: Circulation (2022)

Introduction: High levels of lactate are positively associated with the prognosis and mortality in the patients with acute heart attack and heart failure. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the progression of cardiac fibrosis in multiple cardiovascular diseases. We investigated whether lactate exerts a biological role in EndMT following myocardial infarction (MI). Methods: MI was induced in endothelial cell specific GFP labeled (TIE2GFP) mice by left anterior descending (LAD) coronary artery ligation. To suppress lactate production, 2-Deoxy-D-glucose (2-DG, 2g/kg body weight) was intraperitoneally injected daily for 7 days. Supplemental lactic acid (adjust to pH 6.8, 0.5 g/kg body weight) was administrated to mice either by i.p. injection every 7 days for 1 or 4 weeks or using osmotic mini-pumps after surgery. In vitro , endothelial cells were treated with 5 mM or 10 mM L-lactic acid followed by normoxic or hypoxic challenge in a hypoxia chamber. Results: Our data showed that inhibition of lactate production by 2-DG ameliorated MI induced EndMT, cardiac fibrosis and cardiac dysfunction. On the contrary, administration of supplemental lactate further promoted EndMT and worsened cardiac dysfunction post-MI. In vitro analysis shows that treatment of endothelial cells with lactate decreases the expression of endothelial cell markers and accelerates mesenchymal marker expression, as well as disrupts endothelial cell function and induces mesenchymal like function following hypoxic challenge via activating transforming growth factor-β (TGF-β)/Smad2 signaling pathway. Of note, lactate accelerated the lactylation of Snail1, a transcription factor of TGF-β, promoted its nuclear translocation to bind at the promoter of TGF-β, and upregulated TGF-β expression. Conclusion: In summary, we conclude that lactate acts as an important molecule that upregulates cardiac fibrosis after MI via induction of Snail1 lactylation and nuclear translocation to activate TGF-β/Smad2 pathway, resulting in EndMT.
Abstract 13934: Low Estimated Protein Intake is Associated With Poor Prognosis in Patients With Acute Heart Failure
Authors: Taishi Dotare, Daichi Maeda, Yuya Matsue, Yutaka Nakamura, yuka akama, yuichiro tsujimura, Tsutomu Sunayama, Sayaki Ishiwata, Shoichito Yatsu, Takashi Iso, Takao Kato, Shoko Suda, Masaru Hiki, Takatoshi Kasai, Tohru Minamino
Journal: Circulation (2022)

Introduction: Although a higher protein intake has been related with lower mortality rates in general population, the association between protein intake and nutritional status/mortality in patients with acute heart failure has yet to be clarified. Methods and Results: We retrospectively analyzed 694 patients who were admitted due to acute heart failure in our hospital (mean age, 75±13 years; male 60%). The estimated protein intake was defined as a validated formula: [13.9 + 0.907*body mass index (kg/m 2 ) + 0.0305*urinary urea nitrogen level (mg/dL)] using spot urine samples on admission. All patients were divided into three groups according to the estimated protein intake: low (≤43.6 g/day, n=232), middle (43.7 to 51.5 g/day, n=231), and high (≥51.6 g/day, n=231) group. The primary outcome of this study was regarded as all-cause mortality. Patients with low protein intake were older and had lower albumin compared with other two groups. A lower protein intake was associated with worse nutritional status evaluated using Geriatric Nutritional Risk Index (P&lt;0.001). Kaplan-Meier analysis revealed that the low protein intake group was significantly associated with higher incidence of the primary outcome. Compared to the high protein intake group, Cox proportional hazard analysis demonstrated the low protein intake group was independently associated with all-cause mortality (hazard ratio, 1.80; 95% confidence interval, 1.07-3.02; P=0.026) even after adjustment for confounding factors. Conclusions: Low protein intake was associated with poor nutritional status and all-cause mortality in patients with acute heart failure.
Abstract 13870: Ventricular Fibrillation Arrest in a 27-Year-Old Woman Due to Takotsubo Cardiomyopathy
Authors: Ramez Bodair, W. Savindu Pasan Botheju, Suraj Mishra, Jordana Kron
Journal: Circulation (2022)

Introduction: Sudden cardiac death in young patients may be due to coronary artery disease, primary electrical disease, cardiomyopathy, or congenital anomalies. We explore potential causes for sudden cardiac arrest in a young patient. Case Description: A 27-year-old woman was found unconscious. Initial rhythm showed ventricular fibrillation. Cardiopulmonary resuscitation was done for 5 minutes before return of spontaneous circulation. ECG showed ST elevations in aVL, V4, and V5. She was admitted for therapeutic temperature management. Troponin peaked at 1.86 ng/mL on the evening of arrival. Transthoracic echocardiography (TTE) demonstrated hypokinesis of the mid to distal septum, anterior wall, and apex (Figure 1). Repeat TTE 3 days later showed resolution of the wall motion abnormalities. She reported marijuana use and a domestic dispute with her significant other the night prior. Coronary CT angiography showed calcium score of 0 with normal coronary anatomy, no significant coronary artery stenosis, and incidental finding of bilateral pulmonary artery filling defects. Lower limb venous duplex was unremarkable. Therapeutic dose of enoxaparin was started. Cardiac MRI showed no myocardial infarction, scar, or infiltrative disease. An electrophysiology study revealed adequate QT shortening during epinephrine infusion and no inducible ventricular arrhythmias. Genetic testing was unremarkable. She was discharged with a wearable defibrillator before ultimately receiving a subcutaneous implantable cardioverter-defibrillator. Discussion: The presentation of transient regional wall motion abnormalities, with ST-segment elevations and negative ischemic workup, is highly suggestive of Takotsubo cardiomyopathy, mid-ventricular variant. Marijuana use is a risk factor, and the domestic dispute is a potential emotional trigger. This case highlights Takotsubo cardiomyopathy as a possible cause of sudden cardiac arrest in young patients.
Abstract 14409: Deep Learning Approach for Analyzing Chest X-rays to Predict Cardiac Events in Heart Failure
Authors: Kenya Kusunose, Yukina Hirata, Takumasa Tsuji, Jun'ichi Kotoku, Masataka Sata
Journal: Circulation (2022)

Introduction: A deep learning (DL) model based on a chest X-ray (CXR) was reported to predict elevated pulmonary artery wedge pressure (PAWP) as congestive heart failure (HF). Hypothesis: We hypothesize that a previously developed application of a CXR-based DL algorithm could also be used to predict re-hospitalized HF in patients with HF. This study aimed to 1) investigate the role of probability of elevated PAWP to predict clinical outcomes in association with other parameters, and 2) to evaluate whether probability of elevated PAWP based on DL added prognostic information to other conventional clinical prognostic factors in HF. Methods: We evaluated 192 patients hospitalized with HF. We used a previously developed AI model to predict HF and calculated probability of elevated PAWP in the study cohort. The primary endpoint was readmission following HF and cardiac death. Results: Probability of elevated PAWP was associated with echocardiographic parameters including left atrial size, filling pressure, and pulmonary artery pressure. During a median follow-up period of 58 months, 57 patients were either readmitted or died. Probability of elevated PAWP appeared to be associated with worse clinical outcomes. After adjustment for readmission score and laboratory data in a Cox proportional-hazards model, probability of elevated PAWP at pre-discharge (per 1SD) was associated with event free survival, independent of elevated left atrial pressure (LAP) by echocardiography (hazard ratio:1.39, 95%CI:1.17-1.65, p&lt;0.001). In sequential Cox models, a model based on clinical data (χ2, 16.8) was improved by elevated LAP (χ2,24.4; p =0.005), and increased further by probability of elevated PAWP (χ2,41.1; p &lt;0.001). Conclusions: This study suggests that probability of elevated PAWP provides important incremental prognostic value for predicting readmission and cardiac mortality risk assessment in patients with HF.
Abstract 13420: Association of Digital ECG Biomarkers With Heart Failure Status
Authors: Gabriel Najarro, Louis Li, Erick Andres Perez Alday, Omar Al-Abboud, Blake J Anderson, Ali Bahrami Rad, Chad Robichaux, Gari Clifford, Amit J Shah
Journal: Circulation (2022)

Introduction: Electrocardiography (ECG) may be useful as an adjunct method for evaluating heart failure (HF) severity, but few studies have systematically examined the electrocardiographic parameters associated with heart failure volume status. This may include effects of hypervolemia on thoracic impedance, autonomic function, and subendocardial ischemia. We hypothesized that ECG parameters related to these mechanisms co-vary over time with brain natriuretic peptide, a measure of HF severity. Methods: A retrospective cohort was obtained from the Emory Clinical Data Warehouse for patients who had &gt;2 ECGs performed &gt;3 days apart and repeated BNP measures within 24 hours of each ECG. We quantified the change in HF status by calculating the differences in BNP value between each ECG acquisition time point. A total of 37 metrics were extracted from digitized ECGs as primary predictors and evaluated using multiple linear regression. Results: We evaluated 10,376 pairs of ECGs from 7,171 unique patients. The mean age was 66.9 years, 48% were women, and 51.4% were black . The median absolute change in BNP over time was 178 pg/mL (IQR 52-532), and the median sampling interval was 106 days (IQR 27-357). We evaluated interval, duration, and axis metrics from the P, QRS, and T vectors from the raw digital ECG and found 8 co-varied with BNP changes, including heart rate, P wave axis, QRS amplitude, QRS duration, QRS axis, ST segment, T wave amplitude, and frontal T wave axis (see table). Conclusions: We found several ECG metrics that quantify autonomic activity, depolarization, and repolarization associated with changes in HF status as measured by BNP. These findings may help to understand the downstream effects of hypervolemia on cardiovascular risk and also understand the potential role for certain ECG metrics in helping determine volume status, especially in low-resource settings not offering BNP.
Abstract 14016: Marked Geographic Variation in Atrial Fibrillation Ablation Rates in a Universal Single Payer Health Care System
Authors: Christina Seo, Sameer Kushwaha, Paul Dorian, Timothy Chan, Katherine S Allan, Peter Gozdyra, Husam Abdel Qadir, Paul Angaran
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) ablation is increasingly commonly performed for patients with symptomatic AF. In Canada, AF ablation occurs at specialized electrophysiology centers (“EP centers”), which are clustered in major urban centers. Hypothesis: People with AF who live closer to an EP center are more likely to undergo an AF ablation. Methods: Data was compiled from Ontario Health datasets (e.g. emergency department (ED) visits, hospital discharges, physician billing) and Canadian census data for people presenting to an ED in Ontario, Canada with a new diagnosis of AF between 2007-16. The primary outcome was ablation within one year of the index ED visit. Secondary outcomes include ablation at two years. Multivariate logistic regression was conducted to assess the relationship between distance to EP centers and likelihood of ablation. We also studied ablation frequency in relation to material deprivation (e.g. income, housing quality and education). Geospatial analyses were performed using QGIS. Results: Of the 135,681 people with newly diagnosed AF, 3911 (2.9%) had an ablation within one year of AF diagnosis and 5827 (4.3%) within two. There was a significant inverse relationship between a doubling of distance to the closest EP center and ablation within one year (OR: 0.93, 95% CI: 0.91-0.94), and two years (OR: 0.95, 95% CI: 0.94-0.97). Higher deprivation (measured in standard deviations from the mean) was associated with significantly less ablation at one year (OR: 0.89, 95% CI: 0.85-0.92). There was wide regional variation with relatively low rates near the largest urban center (Figure 1). Conclusions: Living further from an EP center and greater material deprivation are associated with lower AF ablation rates. Ablation rates vary by region, with the highest rates not consistently observed in areas most concentrated with EP centers. Figure 1. Age and sex adjusted AF ablation rates per 100,000 patients within a year of AF diagnosis in Ontario, Canada
Abstract 14188: An Unexpected Cause of Anterior ST Segment Elevation After Coronary Intervention
Authors: Carlos A Requena Armas, Juan Del Cid Fratti, Rimmy Garg, sudhir mungee
Journal: Circulation (2022)

Background: ST elevation (STE) in V1 to V3 is traditionally labeled as anteroseptal infarction due to occlusion of the LAD proximal to the septal branches. An important and uncommon cause for similar ECG findings is an isolated RV myocardial infarction due to occlusion of the proximal RCA and/or its branches. We present a case of anteroseptal ST elevation after jailing of a conus branch during percutaneous coronary intervention (PCI) to the RCA. CASE: 89-year-old female with history of moderate aortic stenosis (AS), hypertension, hypercholesterolemia, and prior stroke presented with progressive dyspnea on exertion and 3 days of chest tightness. Initial echocardiogram showed an EF of 64% and severe AS with peak velocity of 4.27 m/s, mean gradient of 45 mmHg and aortic valve area of 0.43 cm 2 . Coronary angiography showed severe stenosis of the proximal RCA successfully treated with intravascular lithotripsy and drug-eluting stent deployment with jailing of the conus branch. The LAD and LCX had mild nonobstructive disease. Patient developed chest pain after the procedure with new STE in V1 to V3. She was taken for emergent cardiac angiogram due to suspected occlusion of the LAD however this showed unchanged anatomy with patent stent in the RCA and no new severe stenosis or occlusion of the left coronary arteries. There was no flow in the jailed conus branch that was not intervened on due to small vessel size. A repeat echocardiogram showed new mild RV dilatation with unchanged EF and normal LV wall motion. Patient had resolution of the chest pain and STE within 2 hours and was discharged home in stable condition. Conclusion: Occlusion of a conus branch artery with associated isolated RV myocardial infarction is an uncommon cause of STE in anteroseptal leads. High index of suspicion is important to anticipate and manage potential complications like ventricular arrhythmias and RV failure.
Abstract 13201: Sex Difference Following Cardiac-Targeted Irradiation in Mice
Authors: Jason M Dierdorff, Haider Mehdi, Mohamed Elmonzer, Alexander Greiner, William J Kutschke, Jin-young Yoon, Sruti Prathivadhi-Bhayankaram, Gina M Morgan, Peter Wipf, Michael W Epperly, Joel S Greenberger, Barry London
Journal: Circulation (2022)

Introduction: Acute exposure of the heart to ionizing radiation (IR) can damage myocardium, coronary arteries, valves, and pericardium. Long term sequelae include fibrosis, heart failure, arrhythmias and sudden death. We previously reported a protective effect of the oxetanyl sulfoxide radiation mitigator MMS350 in mice treated acutely with 20 Gy total body IR. Here, we assess the long-term effects of cardiac targeted irradiation (CTI) and MMS350 treatment on cardiac structure and function. Methods: Ten week-old C57BL/6J mice (50% male) were exposed to 20 Gy CTI with (+R+D, n=20) or without (+R-D, n=20) MMS350 using an Xstrahl Small Animal Radiation Research Platform and followed for 9 months (mo); a parallel cohort was not irradiated (-R+D, n=10; -R-D, n=10). MMS350 was given in drinking water (0.087 mg/ml) for 10 days before to 9 mo after CTI with one IV injection (20 mg/kg) 30 minutes prior to CTI. Echocardiography (echo) was performed at baseline, 3, 6 and 9 mo. At euthanasia, heart weight (HW), lung weight (LW), body weight (BW) and histology were assessed. Results: CTI led to radiation dermatitis in 3 female mice requiring euthanasia. MMS350 treatment had no significant effect on any parameters. 9 mo after CTI, HW/BW was increased in male but not female mice, while LW/BW was increased in both sexes (Fig 1A-D). Echo showed a significant increase in EDV with CTI in male (p=0.006) but not female mice (Fig 1E-F), along with a trend towards a decrease in EF in male (79±3 vs 86±2%, p=0.11) but not female mice (85±1 vs 86±1%, p=0.59). Trichrome staining demonstrated fibrosis in both male and female hearts (Fig 1G-N). Conclusions: High dose CTI led to cardiac hypertrophy and ventricular dilation after 9 mo in male but not female mice. Both sexes developed cardiac fibrosis and lung congestion. Thus, sex may influence radiation-induced cardiac pathology through currently unknown mechanisms and may have important implications for radiotherapy of thoracic tumors in humans.
Abstract 14318: The Effect of Time-Restricted Eating on Physical Activity: Results From the Time-Restricted Intake of Meals (Trim) Randomized Trial
Authors: Ruth-Alma N Turkson-Ocran, Ryan J Dougherty, Daisy Duan, Scott J Pilla, Jennifer A Schrack, Jeanne M Clark, Nisa M Maruthur
Journal: Circulation (2022)

Introduction: Time-restricted eating (TRE) is a dietary pattern that may promote weight loss by limiting caloric intake, but evidence for its effects on physical activity are limited. Objective: To determine the effect of a TRE pattern compared to a usual eating pattern (UEP) on physical activity. Methods: We examined physical activity data from 41 adults with prediabetes or untreated diabetes (HbA1c 5.7-6.9%) and obesity (BMI 30-50 kg/m 2 ) randomized to consume 80% of their total calories before 1 pm (TRE) or ≥50% of their calories after 5 pm (UEP) with identical macronutrient content. Participants were fitted with a wrist-worn GT9X accelerometer (Actigraph; Pensacola FL) to measure free-living physical activity behaviors for one week at baseline and 12 weeks. Outcomes were mean total activity counts (measure of activity volume and intensity) and time spent active (measure of activity volume) per day. We used linear mixed effects regression models with participant-specific random intercepts to examine the difference in outcomes between the two groups from baseline to 12 weeks; the intervention-by-time interaction was the term of interest (β int ). Results: Thirty-nine adults (mean age 59.5 years; 92% female; 92% African American) completed actigraphy assessments. We observed a significant decrease in all physical activity measures from baseline to 12 weeks in TRE, but not in UEP ( Table ). Total activity counts (p for β int =0.005), but not time spent active (p for β int =0.094) declined significantly in TRE compared to UEP. Conclusion: In this randomized feeding study, TRE was associated with reduced physical activity intensity while overall physical activity volume was unaffected, compared to a UEP. This unexpected compensatory decrease in physical activity intensity may limit the efficacy of TRE for achieving weight loss. Future studies are needed to understand the mechanisms behind this effect, and to optimize TRE interventions to maintain physical activity levels.
Abstract 13582: Biomarkers of Adverse Cardiovascular Events in Chronic Coronary Disease: Data From the ISCHEMIA Trial
Authors: Jonathan D Newman, Kelly V Ruggles, Macintosh Cornwell, Rebecca Anthopolos, Claes Held, Iftikhar J Kullo, L Kristin K Newby, Bruce M McManus, Sripal Bangalore, Harmony R Reynolds, Judith S Hochman, David J Maron, Jeffrey S Berger
Journal: Circulation (2022)

Introduction: Circulating biomarkers may improve prediction of cardiovascular (CV) events in chronic coronary disease (CCD). The incremental value of biomarkers in CCD after adjustment for clinical factors, inducible ischemia and coronary artery disease (CAD) severity is uncertain. Methods: 756 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) participants with site-determined moderate-severe ischemia and 9 assayed biomarkers (Figure) were included. Among participants with interpretable stress tests for ischemia and CAD by computed coronary tomography angiography (CCTA) (N=507), associations of biomarkers with the primary (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) or secondary endpoints (CV death or MI) were evaluated using sequentially adjusted multivariable Cox proportional hazards models (Model 1=unadjusted, Model 2=clinical features, Model 3=Model 2 + multivessel CAD by CCTA, and Model 4=Model 3 + severe ischemia). Results: Median (IQR) participant age was 64 (57-70) years, 19% were female, 81% white, and 5% Hispanic. Hypertension (85%), diabetes (46%) and obesity (45%) were common, 28% had an estimated glomerular filtration rate &lt;60 ml/min/1.73m 2 . Severe ischemia was present in 44%, and 39% had multivessel CAD (≥70% stenosis) by CCTA. Over 3.5 (2.4-4.7) years of follow-up there were 146 (19%) primary and 128 (17%) secondary endpoints. Soluble CD40L, GDF-15, NT-proBNP, hsTnT were associated with the primary and secondary endpoints in univariable and multivariable (adjusting for clinical features, multivessel CAD and severe ischemia) models. Conclusion: Biomarkers of inflammation (GDF-15), thrombosis (sCD40L), myocardial stretch (NT-proBNP) and injury (hs-troponin) were associated with CV endpoints in the ISCHEMIA trial independent of clinical features, multivessel CAD and severe ischemia.
Abstract 13291: Virtual Pharmacist Approach to Comprehensive Medication Management in Post-Discharge Heart Failure Patients: A Randomized Quality Improvement Initiative
Authors: Tram Thai, Greg Downing, Melanie Plotke, Eric Olmsted, Farrukh Jafri
Journal: Circulation (2022)

Introduction: Successful management of Heart Failure (HF) patients post-discharge requires a multi-faceted approach including close medication management to decrease preventable readmissions. Methods: We conducted a one-year single center, single-blinded randomized trial of HF patients post-discharge comparing standard of care vs. intensive virtual care on HF readmission rates. The intensive virtual care included comprehensive medication management by a Virtual Clinical Pharmacist (VCP). Results: Among the 591 participants, the median age was 73.2 years, 52.5% male, and 56.2% white. There were 308 patients randomized into the intervention group of which 165 (53.5%) enrolled. During VCP visits, 155 patient concerns were identified including active symptoms (45.2%), lack of clarity of medication regimen (40.6%), concurrent uncontrolled hyperglycemia or hypertension (9%) and non-adherence with provider follow up appointments (5.2%). There were 625 VCP interventions in 165 HF patients. Of these patients, VCPs increased access to medical care (33.9%), optimized guideline directed medical therapy (17.6%), addressed symptoms of HF exacerbations (7.9%), and other impactful interventions (Table). VCP recommendations had a 59% acceptance rate into the patient’s treatment plan when clinicians were contacted directly. A 6.9% decrease in 30-day readmission rates was demonstrated (p=0.03) in the intervention group, in addition to a decrease from 24.4% to 19.2% in emergency department visits (p=0.15). For patients readmitted, the intervention arm had a shorter length of stay, 5.6 days, when compared to control, 6.8 days (p=0.14). Conclusion: This single center randomized trial demonstrated that Virtual Clinical Pharmacist-led comprehensive medication management identified key interventions with high-level clinician engagement for post-discharge HF patients that resulted in a 6.9% reduction in HF readmissions.